1,139 research outputs found

    An Acute Evolving Flaccid Quadriparesis in an Elderly Woman

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    Andrew Larner and colleagues discuss the differential diagnosis, investigation, and management of a 72-year-old woman presenting with progressive lower limb weakness who develops an acute evolving flaccid quadriparesis

    Amnion Epithelial Cells as a Candidate Therapy for Acute and Chronic Lung Injury

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    Acute and chronic lung injury represents a major and growing global burden of disease. For many of these lung diseases, the damage is irreparable, exhausting the host's ability to regenerate new lung, and current therapies are simply supportive rather than restorative. Cell-based therapies offer the promise of tissue regeneration for many organs. In this paper, we examine the potential application of amnion epithelial cells, derived from the term placenta, to lung regeneration. We discuss their unique properties of plasticity and immunomodulation, reviewing the experimental evidence that amnion epithelial cells can prevent and repair lung injury, offering the potential to be applied to both neonatal, childhood, and adult lung disease. It is amazing to suggest that the placenta may offer renewed life after birth as well as securing new life before

    The qTq_T spectrum for Higgs production via heavy quark annihilation at N3^3LL'+aN3^3LO

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    We study the transverse momentum (qTq_T) spectrum of the Higgs boson produced via the annihilation of heavy quarks (s,c,bs,c,b) in proton-proton collisions. Using soft-collinear effective theory (SCET) and working in the five-flavour scheme, we provide predictions at three-loop order in resummed perturbation theory (N3^3LL'). We match the resummed calculation to full fixed-order results at next-to-next-to-leading order (NNLO), and introduce a decorrelation method to enable a consistent matching to an approximate N3^3LO (aN3^3LO) result. Since the bb-quark initiated process exhibits large nonsingular corrections, it requires special care in the matching procedure and estimation of associated theoretical uncertainties, which we discuss in detail. Our results constitute the most accurate predictions to date for these processes in the small qTq_T region and could be used to improve the determination of Higgs Yukawa couplings from the shape of the measured Higgs qTq_T spectrum.Comment: 25 pages + 11 appendix + references, 18 figure

    Preliminary Characterization of Voltage-Activated Whole-Cell Currents in Developing Human Vestibular Hair Cells and Calyx Afferent Terminals

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    We present preliminary functional data from human vestibular hair cells and primary afferent calyx terminals during fetal development. Whole-cell recordings were obtained from hair cells or calyx terminals in semi-intact cristae prepared from human fetuses aged between 11 and 18 weeks gestation (WG). During early fetal development (11–14 WG), hair cells expressed whole-cell conductances that were qualitatively similar but quantitatively smaller than those observed previously in mature rodent type II hair cells. As development progressed (15–18 WG), peak outward conductances increased in putative type II hair cells but did not reach amplitudes observed in adult human hair cells. Type I hair cells express a specific low-voltage activating conductance, G(K,L). A similar current was first observed at 15 WG but remained relatively small, even at 18 WG. The presence of a “collapsing” tail current indicates a maturing type I hair cell phenotype and suggests the presence of a surrounding calyx afferent terminal. We were also able to record from calyx afferent terminals in 15–18 WG cristae. In voltage clamp, these terminals exhibited fast inactivating inward as well as slower outward conductances, and in current clamp, discharged a single action potential during depolarizing steps. Together, these data suggest the major functional characteristics of type I and type II hair cells and calyx terminals are present by 18 WG. Our study also describes a new preparation for the functional investigation of key events that occur during maturation of human vestibular organs

    The effect of human amnion epithelial cells on lung development and inflammation in preterm lambs exposed to antenatal inflammation

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    Lung inflammation and impaired alveolarization are hallmarks of bronchopulmonary dysplasia (BPD). We hypothesize that human amnion epithelial cells (hAECs) are anti-inflammatory and reduce lung injury in preterm lambs born after antenatal exposure to inflammation. Pregnant ewes received either intra-amniotic lipopolysaccharide (LPS, from E.coli 055:B5 4mg) or saline (Sal) on day 126 of gestation. Lambs were delivered by cesarean section at 128 d gestation (term ~150 d). Lambs received intravenous hAECs (LPS/hAECs: n = 7 30x10.sup.6 cells) or equivalent volumes of saline (LPS/Sal, n = 10 or Sal/Sal, n = 9) immediately after birth. Respiratory support was gradually de-escalated, aimed at early weaning from mechanical ventilation towards unassisted respiration. Lung tissue was collected 1 week after birth. Lung morphology was assessed and mRNA levels for inflammatory mediators were measured. Respiratory support required by LPS/hAEC lambs was not different to Sal/Sal or LPS/Sal lambs. Lung tissue:airspace ratio was lower in the LPS/Sal compared to Sal/Sal lambs (P<0.05), but not LPS/hAEC lambs. LPS/hAEC lambs tended to have increased septation in their lungs versus LPS/Sal (P = 0.08). Expression of inflammatory cytokines was highest in LPS/hAECs lambs. Postnatal administration of a single dose of hAECs stimulates a pulmonary immune response without changing ventilator requirements in preterm lambs born after intrauterine inflammation

    Heterogeneous Responses to Antioxidants in Noradrenergic Neurons of the Locus Coeruleus Indicate Differing Susceptibility to Free Radical Content

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    The present study investigated the effects of the antioxidants trolox and dithiothreitol (DTT) on mouse Locus coeruleus (LC) neurons. Electrophysiological measurement of action potential discharge and whole cell current responses in the presence of each antioxidant suggested that there are three neuronal subpopulations within the LC. In current clamp experiments, most neurons (55%; 6/11) did not respond to the antioxidants. The remaining neurons exhibited either hyperpolarization and decreased firing rate (27%; 3/11) or depolarization and increased firing rate (18%; 2/11). Calcium and JC-1 imaging demonstrated that these effects did not change intracellular Ca2+ concentration but may influence mitochondrial function as both antioxidant treatments modulated mitochondrial membrane potential. These suggest that the antioxidant-sensitive subpopulations of LC neurons may be more susceptible to oxidative stress (e.g., due to ATP depletion and/or overactivation of Ca2+-dependent pathways). Indeed it may be that this subpopulation of LC neurons is preferentially destroyed in neurological pathologies such as Parkinson's disease. If this is the case, there may be a protective role for antioxidant therapies

    Heterogeneous Responses to Antioxidants in Noradrenergic Neurons of the Locus Coeruleus Indicate Differing Susceptibility to Free Radical Content

    Get PDF
    The present study investigated the effects of the antioxidants trolox and dithiothreitol (DTT) on mouse Locus coeruleus (LC) neurons. Electrophysiological measurement of action potential discharge and whole cell current responses in the presence of each antioxidant suggested that there are three neuronal subpopulations within the LC. In current clamp experiments, most neurons (55%; 6/11) did not respond to the antioxidants. The remaining neurons exhibited either hyperpolarization and decreased firing rate (27%; 3/11) or depolarization and increased firing rate (18%; 2/11). Calcium and JC-1 imaging demonstrated that these effects did not change intracellular Ca2+ concentration but may influence mitochondrial function as both antioxidant treatments modulated mitochondrial membrane potential. These suggest that the antioxidant-sensitive subpopulations of LC neurons may be more susceptible to oxidative stress (e.g., due to ATP depletion and/or overactivation of Ca2+-dependent pathways). Indeed it may be that this subpopulation of LC neurons is preferentially destroyed in neurological pathologies such as Parkinson's disease. If this is the case, there may be a protective role for antioxidant therapies

    Simulating spatial and temporal evolution of multiple wing cracks around faults in crystalline basement rocks

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    Fault zones are structurally highly spatially heterogeneous and hence extremely complex. Observations of fluid flow through fault zones over several scales show that this structural complexity is reflected in the hydrogeological properties of faults. Information on faults at depth is scarce, hence, it is highly valuable to understand the controls on spatial and temporal fault zone development. In this paper we increase our understanding of fault damage zone development in crystalline rocks by dynamically simulating the growth of single and multiple splay fractures produced from failure on a pre-existing fault. We present a new simulation model, MOPEDZ (Modeling Of Permeability Evolution in the Damage Zone surrounding faults), that simulates fault evolution through solution of Navier's equation with a combined Mohr-Coulomb and tensile failure criteria. Simulations suggest that location, frequency, mode of failure and orientation of splay fractures are significantly affected both by the orientation of the fault with respect to the maximum principal compressive stress and the conditions of differential stress. Model predictions compare well with published field outcrop data, confirming that this model produces realistic damage zone geometries

    Personal and reported partner pornography viewing by Australian women, and association with mental health and body image

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    Background: Personal and partner pornography viewing may affect health and wellbeing. This study aimed to improve understanding of the effects of pornography on mental health and body image, given emerging evidence of increasing use, particularly among young people. Methods: A cross-sectional survey was implemented, targeting people who had accessed health and fitness content via social media. Convenience sampling was used and participants were recruited via advertising on social media. Results: Overall, 76% (75/99) of women reported having ever viewed pornography, and 21% had viewed pornography frequently (monthly/weekly/daily) in the prior 12 months. The association between frequent viewing and higher-risk Kessler 10 Psychological Distress Scale scores lost significance once controlled for age (adjusted OR 2.30, 95%CI 0.82–6.49, P = 0.11). There was an association with frequent reported partner pornography use (monthly/weekly/daily) and increased Drive for Muscularity scores (adjusted OR 2.20, 95%CI 1.01–4.80, P = 0.048). There were no other associations found with pornography use (personal or partner) and body image or mental health, although this was limited by the small sample size. Most women (85%, 41/48) reported being happy with their partner’s pornography use, and in qualitative responses, indicated that pornography had minimal effect on their lives. Nevertheless, multiple qualitative responses indicated a multiplicity of perceived effects of pornography, including negative effects on body image. Conclusions: Pornography had a minor effect on mental health and body image in this study. Additional research is required to improve understanding of the effects of pornography on body image and mental health, particularly among vulnerable individuals
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